Figure 2.

Role of miR-9 in the development of drosophila sensory organs. (A) Different steps of the formation of sensory organs. Among the ectodermal tissue, groups of cells, called proneural clusters (green), acquire neural competence via the induction of proneural genes. The dLMO protein participates in the acquisition of this competence. Among competent cells, one will maintain high levels of proneural genes expression, notably of the sense gene, and become a SOP cell (SOP, yellow). Concomitantly the neural fate is inhibited in the neighboring cells (non-SOP, blue). The SOP cell later divides to give rise to a sensory organ. miR-9a is present in all ectodermal cells except the SOP cell, and inhibits dLMO and Sens protein expression. (B) Role of miR-9a in SOP cell specification. The SOP cell expresses high levels of the ligand Delta, which interacts with Notch receptors located at the surface of neighboring cells. This interaction leads to Notch cleavage, which releases Notch intracellular domain (N^intra) in non-SOP cells. N^intra interacts with the transcription factor Suppressor of Hairless Su(H), which induces E(spl) gene expression. E(spl) genes encode transcriptional repressors inhibiting the expression of proneural genes and in particular sens. In the SOP cell, in the absence of N^intra, Su(H) has an inhibitory effect on the transcription of E(spl) genes which allows for the expression of sens. Sens activates the expression of proneural genes of the ac/scute complex (ac/sc) which specify the SOP cell fate. miR-9a, expressed in non-SOP cells, prevents ectopic expression of sens, thereby conferring robustness to the developmental program. Other genes of the miR-9 family might also play a role here, as miR-4 and miR-79 have been shown to regulate the expression Notch target genes, such as E(spl) or Brd.